2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → 3-(3-{3-[4-(4-Biphenyl-2-ylmethyl-piperazin-1-yl)-benzyl]-2-imino-2,3-dihydro-benzoimidazol-1-yl}-propoxy)-benzoic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

To a mixture of 3-{3-[3-(4-bromo-benzyl)-2-imino-2,3-dihydro-benzoimidazol-1-yl]-propoxy}-benzoic acid ethyl ester (0.50 g, 0.99 mmol), sodium tert-butoxide (0.26 g, 2.67 mmol), 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (33 mg, 0.07 mmol) and Pd(OAc)2 (22 mg, 0.10 mmol) at rt was added a degassed solution of 1-biphenyl-2-ylmethyl-piperazine (0.25 g, 0.99 mmol) in toluene (15 ml) and tert-butanol (3 ml). The reaction was heated to 120° C. where it was maintained fro 3 d. After this time, the reaction was cooled to rt and concentrated under reduced pressure. The material that remained was partitioned between H2O and EtOAc and the organic phase was separated, dried (Na2SO4), filtered and concentrated under reduced pressure. Purification by chromatography on silica eluting with EtOAc/hexane provided 3-(3-{3-[4-(4-biphenyl-2-ylmethyl-piperazin-1-yl)-benzyl]-2-imino-2,3-dihydro-benzoimidazol-1-yl}-propoxy)-benzoic acid ethyl ester (42 mg, 6%). HPLC-MS 680 [M+1]+, 341.

Provenance & Evidence